David Glance

Prostaglandin production and stimulation by angiotensin II in the isolated perfused human placental cotyledon

Levels of prostaglandins E and F2 alpha, thromboxane B2, and 6-oxo-prostaglandin F1 alpha were measured by radioimmunoassay in the maternal and fetal effluents of isolated human placental cotyledons perfused in vitro. All prostaglandins measured were released in greater amounts by the maternal side than by the fetal side of the perfused cotyledon although there were no consistent concentration gradients between the two sides. The approximate rank order of prostaglandin release into the maternal side was thromboxane B2 greater than prostaglandin F2 alpha congruent to prostaglandin E congruent to 6-oxo-prostaglandin F1 alpha, and that into the fetal side was thromboxane B2 congruent to prostaglandin F2 alpha congruent to prostaglandin E congruent to 6-oxo-prostaglandin F1 alpha. Injection of angiotensin II (0.5 microgram) into the fetal circulation stimulated prostaglandin E and 6-oxo-prostaglandin F1 alpha but not thromboxane B2 and prostaglandin F2 alpha release into the fetal circulation and had no effect on maternal release. Angiotensin II (0.5 microgram) had no effect on either side of the perfused cotyledon when injected into the maternal circulation. It is proposed that prostaglandin release into both maternal and fetal circulations may be flow-dependent and that the angiotensin II-stimulated release of prostaglandin E and 6-oxo-prostaglandin F1 alpha may serve to modulate the vasoactive actions of angiotensin II on the fetal vasculature.

The actions of prostaglandins and their interactions with angiotensin II in the isolated perfused human placental cotyledon

Summary. The prostaglandins PGE1, PGE 2, PGD 2, PGF 2α., U46619 and 6β‐PGIl were administered as bolus injections both separately and in combination with angiotensin II into the fetal circulation of isolated human placental cotyledons perfused in vitro. PGF2α, and PGD2, caused small dosedependent increases in fetal perfusion pressure when compared with U46619 which acted as an extremely potent vasoconstrictor of the fetal‐placental vasculature. PGE1, caused very small dose‐dependent decreases in fetal perfusion pressure when injected on its own. In combination with angiotensin 11, PGE1, PGD2, and 6β‐PG11, caused significant, dose‐related attenuations of the angiotensin II vasoconstrictive response whereas PGE2, PGF2α, and U46619 potentiated the response. Injections of angiotensin II after the infusion of indomethacin into the fetal circulation resulted in a potentiation of angiotensin II induced vasoconstriction. The results indicate that prostaglandins exert their effects on the fetal‐placental circulation by modulating the actions of angiotensin II.

The effects of the components of the renin-angiotensin system on the isolated perfused human placental cotyledon

Angiotensins I, II, and III, renin substrate, and des-Asp1-angiotensin I were injected as a bolus into either the maternal or fetal circulation of human placental cotyledons perfused in vitro. All drugs tested produced dose-related increments in fetal perfusion pressure when injected into the fetal circulation, with the order of potency being angiotensin I approximately equal to angiotensin II approximately equal to angiotensin III greater than or equal to des-Asp1-angiotensin I greater than or equal to renin substrate. The responses to all the drugs could be blocked by the competitive inhibitor of angiotensin II, (Sar1, Ala8)-angiotensin II, but only the actions of angiotensin I, renin substrate, and des-Asp1-angiotensin I could be blocked by angiotensin converting enzyme inhibitor. When the agents were injected into the maternal circulation, only angiotensins II and III caused dose-related increments in fetal perfusion pressure. Possibly, the placenta may be the main site of conversion of angiotensin I to angiotensin II in the fetoplacental unit, and angiotensin II produced by the placenta could act locally to control fetoplacental blood flow.

Flipping the sociology classroom: Towards a practice of online pedagogy

Profound changes are under way in university learning and teaching. Online education is taking hold as never before, catalysed in no small part by the advent of Massive Open Online Courses (MOOCs), free university units offered online to anyone with an internet connection. MOOCs appear to be intensifying the trend towards ‘flipping’ the classroom, which involves students engaging with course materials online – usually short videos and readings – then coming to classes constructed as workshops or symposia in which they are invited to practically apply their new knowledge in a variety of ways. This article reports on the ways in which MOOCs have allowed us to critically re-examine pedagogy and practice in the sociology classroom and to test our own assumptions regarding effective pedagogy via an action research project interrogating student reception of a flipped sociology class. Based on preliminary surveys, participant observation and formal interviews gauging student perceptions and initial reception to this particular class, the research reported here offers important correctives to debates that are usually based more on supposition than empirical evidence.

Developing cancer warning statements for alcoholic beverages

BackgroundThere is growing evidence of the increased cancer risk associated with alcohol consumption, but this is not well understood by the general public. This study investigated the acceptability among drinkers of cancer warning statements for alcoholic beverages.MethodsSix focus groups were conducted with Australian drinkers to develop a series of cancer-related warning statements for alcohol products. Eleven cancer warning statements and one general health warning statement were subsequently tested on 2,168 drinkers via an online survey. The statements varied by message frame (positive vs negative), cancer reference (general vs specific), and the way causality was communicated (‘increases risk of cancer’ vs ‘can cause cancer’).ResultsOverall, responses to the cancer statements were neutral to favorable, indicating that they are unlikely to encounter high levels of negative reaction from the community if introduced on alcoholic beverages. Females, younger respondents, and those with higher levels of education generally found the statements to be more believable, convincing, and personally relevant. Positively framed messages, those referring to specific forms of cancer, and those using ‘increases risk of cancer’ performed better than negatively framed messages, those referring to cancer in general, and those using the term ‘can cause cancer’.ConclusionCancer warning statements on alcoholic beverages constitute a potential means of increasing awareness about the relationship between alcohol consumption and cancer risk.

Uptake, transfer and metabolism of prostaglandin E2 in the isolated perfused human placental cotyledon.

(3H) PGE2 uptake and transfer in the isolated perfused human placental cotyledon was assessed by a single pass paired isotope dilution technique utilising (14C) sucrose as an extracellular marker. Metabolism of (3H) PGE2 was measured by analysing maternal and fetal effluents from perfused human placental cotyledons after bolus injection of (3H) PGE2 into either the maternal or fetal sides. Maximal uptake of (3H) PGE2 was greater on the maternal (81 +/- 8%) than the fetal sides (42 +/- 12%) and showed saturation with increasing concentrations of PGE2 only on the fetal side with an apparent Km of 12 +/- 4.9 nmol/l and vmax of 1.5 +/- 0.2 pmol/min/g. Total recoveries of (3H) PGE2 were 84.6 +/- 11.8% and 32.6 +/- 6.3% of the injected dose after injection on the fetal and maternal sides respectively. Transfer of (3H) PGE2 was the same in both directions being 6.4 +/- 1.2% of the injected dose in the fetal-maternal direction and 5.8 +/- 2.7% of the injected dose in the maternal-fetal direction. Metabolism was greater on the maternal side (35% of injected (3H) PGE2) than the fetal side (18% of injected (3H) PGE2) and was principally to the 13,14-dihydro-15-keto-PGE2 metabolite. Metabolism of (3H) PGE2 after passage across the placenta was the same in both directions and was of the order of approximately 60%.

Implementing a QCancer risk tool into general practice consultations: an exploratory study using simulated consultations with Australian general practitioners

Background:Reducing diagnostic delays in primary care by improving the assessment of symptoms associated with cancer could have significant impacts on cancer outcomes. Symptom risk assessment tools could improve the diagnostic assessment of patients with symptoms suggestive of cancer in primary care. We aimed to explore the use of a cancer risk tool, which implements the QCancer model, in consultations and its potential impact on clinical decision making.Methods:We implemented an exploratory ‘action design’ method with 15 general practitioners (GPs) from Victoria, Australia. General practitioners applied the risk tool in simulated consultations, conducted semi-structured interviews based on the normalisation process theory and explored issues relating to implementation of the tool.Results:The risk tool was perceived as being potentially useful for patients with complex histories. More experienced GPs were distrustful of the risk output, especially when it conflicted with their clinical judgement. Variable interpretation of symptoms meant that there was significant variation in risk assessment. When a risk output was high, GPs were confronted with numerical risk outputs creating challenges in consultation.Conclusions:Significant barriers to implementing electronic cancer risk assessment tools in consultation could limit their uptake. These relate not only to the design and integration of the tool but also to variation in interpretation of clinical histories, and therefore variable risk outputs and strong beliefs in personal clinical intuition.

Impact of a Digital Activity Tracker-Based Workplace Activity Program on Health and Wellbeing

Chronic disease is endemic within the Australian community. 3.6 million Australians have diabetes or pre-diabetes with the number increasing by 7% each year. Fifty three percent of Australians have one or more chronic diseases. Increasing levels of activity has proved relatively straightforward, especially through workplace physical activity interventions. What is still not certain are the short, and long-term, health benefits arising from these workplace activity challenges. Research into workplace activity challenges is beset with a number of methodological obstacles that may, in part, explain why consistent outcomes have not been found from studies of this type. The aim of this study was to assess whether participation in a 16-week activity challenge would result in measurable changes in lipid profile, blood glucose, renal function, blood pressure, weight and health and well being as measured using a health and wellbeing assessment. The study demonstrated that participants could increase their levels of activity and maintain at least 10,000 steps a day for a period of 16 weeks. The study also identified that participants in teams were significantly more active than those participating as individuals. Furthermore, attrition from the activity challenge was greater amongst participants not in a team. This demonstrated the importance of social interactions, support and possibly other factors that being part of a group brought to the experience of participating in the activity challenge. In addition to the above, the challenge resulted in reductions in non-HDL cholesterol, and triglyceride concentrations and health and well being score.

Australian drinkers’ perceptions of alcohol-related risk by consumption status

Abstract Background: This study investigated Australian drinkers’ alcohol-related beliefs according to their alcohol risk status. The primary aims were to assess drinkers’ awareness of the association between alcohol consumption and a range of health consequences and their understanding of the degree of risk represented by their own alcohol consumption. Method: An online survey was administered to 2168 drinkers who consume alcohol at least twice per month. Respondents reported their alcohol intake levels and their beliefs relating to the relationship between alcohol and shorter-term (proximal) risks (e.g., drink-driving) and longer-term (distal) risks (e.g., stroke and cancer). Results: Just over half (52%) of those drinking at high or very high risk levels did not perceive their drinking to be harmful. A large majority (85%) of the sample was aware of various short-term risks of excessive alcohol consumption, but only half appeared aware of the association between alcohol consumption and more distal health conditions. Conclusions: The relatively low levels of awareness of the alcohol–disease link and the weak relationship between perceived risk and alcohol consumption levels suggest that attempts to reduce current high levels of alcohol-related harm could include public education campaigns designed to (i) improve drinkers’ understanding of the prevalence of alcohol-related harms upon which current alcohol guidelines are based, (ii) prompt drinkers to review their intake levels in the light of the guidelines to assess their potential risk of harm, and (iii) make alcohol-related risks more salient to every-day consumption decisions.

Cognitive bias modification to prevent depression (COPE): study protocol for a randomised controlled trial

BackgroundDepression is a leading cause of disability worldwide and, although efficacious treatments are available, their efficacy is suboptimal and recurrence of symptoms is common. Effective preventive strategies could reduce disability and the long term social and health complications associated with the disorder, but current options are limited. Cognitive bias modification (CBM) is a novel, simple, and safe intervention that addresses attentional and interpretive biases associated with anxiety, dysphoria, and depression. The primary aim of this trial is to determine if CBM decreases the one-year onset of a major depressive episode among adults with subsyndromal depression.Design and methodsThis randomised controlled trial will recruit 532 adults with subsyndromal symptoms of depression living in the Australian community (parallel design, 1:1 allocation ratio). Participants will be free of clinically significant symptoms of depression and of psychotic disorders, sensory and cognitive impairment, and risky alcohol use. The CBM intervention will target attentional and interpretive biases associated with depressive symptoms. The sessions will be delivered via the internet over a period of 52 weeks. The primary outcome of interest is the onset of a major depressive episode according the DSM-IV-TR criteria over a 12-month period. Secondary outcomes of interest include change in the severity of depressive symptoms as measured by the Patient Health Questionnaire (PHQ-9), use of antidepressants or benzodiazepines, and changes in attention and interpretive biases. The assessment of outcomes will take place 3, 6, 9, and 12 months after randomisation and will occur via the internet.DiscussionWe propose to test the efficacy of an innovative intervention that is well grounded in theory and for which increasing empirical evidence for an effect on mood is available. The intervention is simple, inexpensive, easy to access, and could be easily rolled out into practice if our findings confirm a role for CBM in the prevention of depression.Trial registrationAustralian and New Zealand Clinical Trials Registry ACTRN12613001334796. Date: 5th December 2013.